Myricetin and its derivative M10, myricetin-3-O-β-d-lactose sodium salt, modify the composition of gut microbiota in mice with chronic ulcerative colitis

Abstract Background Previous studies revealed that Myricetin and derivative M10, Myricetin-3-O-β-d-lactose sodium salt, prevented chronic ulcerative colitis (UC) in mice. We investigated whether the inhibitory effects of Myricetin and M10 on UC were associated to the modification of intestinal microbiota. Samples of intestinal microbiota were collected from the ileocecum of UC mice which demonstrated response to the treatment of Myricetin and M10. Gut microbiota was analyzed by 16S rDNA sequencing assay. Results UC model mice demonstrated the increases of Firmicutes and Actinobacteria as compared to healthy control mice. Oral M10 and Myricetin normalized the composition of Firmicutes and Actinobacteria. At genus level, the effect of M10 and Myricetin on ulcerative colitis was strongly associated to the increase of probiotics, such as Akkermansia, and the inhibition of pathogenic microorganisms, such as Ruminococcus and Parabacteroides. Myricetin’s derivative M10 significantly increased both biosynthesis and degradation activities, resulting to strong improvements of the metabolism of sulfur, pyruvate, steroid biosynthesis and unsaturated fatty acid biosynthesis in gut microenvironment. Conclusions Natural product Myricetin and its derivative M10 could modify the modification of gut microbiota in UC mice. Combined with pharmacologic effects of Myricetin and M10 in these UC mice, we conclued that the effects of Myricetin and M10 on UC were associated to the modification of intestinal microbiota in the environment of chronic ulcerative colitis.

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Integrated Fecal Microbiome and Serum Metabolomics Analysis Reveals Abnormal Changes in Rats with Immunoglobulin A Nephropathy and the Intervention Effect of Zhen Wu Tang

Frontiers in Pharmacology ◽

10.3389/fphar.2020.606689 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jicheng Li ◽

Yiwen Cao ◽

Ruirui Lu ◽

Honglian Li ◽

Yu Pang ◽

...

Keyword(s):

Gut Microbiota ◽

Renal Disease ◽

Intestinal Microbiota ◽

Renal Damage ◽

Immunoglobulin A ◽

Metabolic Phenotype ◽

Immunoglobulin A Nephropathy ◽

Metabolic Phenotypes ◽

Potential Relationship ◽

Rdna Sequencing

Immunoglobulin A nephropathy (IgAN), an autoimmune renal disease with complicated pathogenesis, is one of the principal reasons for end-stage renal disease in the clinic. Evidence has linked apparent alterations in the components of the microbiome and metabolome to renal disease in rats. However, thus far, there is insufficient evidence that supports the potential relationship between gut microbiome, circulating metabolites, and IgAN. This study was designed to probe the effects of IgAN on intestinal microecology and metabolic phenotypes and to understand the possible underlying mechanisms. Fecal and serum samples were collected from IgAN rats. Composition of the gut microbiota and biochemical changes in the metabolites was analyzed using 16S rDNA sequencing and untargeted metabolomics. The IgAN rats exhibited renal insufficiency and increased concentration of 24-h urine protein, in addition to deposition of IgA and IgG immune complexes in the kidney tissues. There was a disturbance in the balance of gut microbiota in IgAN rats, which was remarkably associated with renal damage. Marked changes in microbial structure and function were accompanied by apparent alterations in 1,403 serum metabolites, associated with the disorder of energy, carbohydrate, and nucleotide metabolisms. Administration of Zhen Wu Tang ameliorated microbial dysbiosis and attenuated the renal damage. Besides, treatment with Zhen Wu Tang modulated the metabolic phenotype perturbation in case of gut microbiota dysbiosis in IgAN rats. In conclusion, these findings provided a comprehensive understanding of the potential relationship between the intestinal microbiota and metabolic phenotypes in rats with IgAN. Elucidation of the intestinal microbiota composition and metabolic signature alterations could identify predictive biomarkers for disease diagnosis and progression, which might contribute to providing therapeutic strategies for IgAN.

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Intestinal Microbiota as Modulators of the Immune System and Neuroimmune System: Impact on the Host Health and Homeostasis

Journal of Immunology Research ◽

10.1155/2015/931574 ◽

2015 ◽

Vol 2015 ◽

pp. 1-14 ◽

Cited By ~ 49

Author(s):

Carlos Magno da Costa Maranduba ◽

Sandra Bertelli Ribeiro De Castro ◽

Gustavo Torres de Souza ◽

Cristiano Rossato ◽

Francisco Carlos da Guia ◽

...

Keyword(s):

Multiple Sclerosis ◽

Ulcerative Colitis ◽

Immune System ◽

Gut Microbiota ◽

Intestinal Microbiota ◽

Present Review ◽

Present Moment ◽

Depression And Anxiety ◽

Neuroimmune System ◽

Host Health

Many immune-based intestinal disorders, such as ulcerative colitis and Crohn’s disease, as well as other illnesses, may have the intestines as an initial cause or aggravator in the development of diseases, even apparently not correlating directly to the intestine. Diabetes, obesity, multiple sclerosis, depression, and anxiety are examples of other illnesses discussed in the literature. In parallel, importance of the gut microbiota in intestinal homeostasis and immunologic conflict between tolerance towards commensal microorganisms and combat of pathogens is well known. Recent researches show that the immune system, when altered by the gut microbiota, influences the state in which these diseases are presented in the patient directly and indirectly. At the present moment, a considerable number of investigations about this subject have been performed and published. However, due to difficulties on correlating information, several speculations and hypotheses are generated. Thus, the present review aims at bringing together how these interactions work—gut microbiota, immune system, and their influence in the neuroimmune system.

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Effects of Xylo-Oligosaccharide on the Gut Microbiota of Patients With Ulcerative Colitis in Clinical Remission

Frontiers in Nutrition ◽

10.3389/fnut.2021.778542 ◽

2021 ◽

Vol 8 ◽

Author(s):

Zongwei Li ◽

Zhengpeng Li ◽

Liying Zhu ◽

Ning Dai ◽

Gang Sun ◽

...

Keyword(s):

Ulcerative Colitis ◽

Gut Microbiota ◽

Healthy Volunteers ◽

Clinical Remission ◽

Principal Component ◽

Fecal Samples ◽

Linear Discriminant ◽

Wilcoxon Rank Sum Test ◽

Rdna Sequencing

Gut microbiota dysbiosis is closely associated with ulcerative colitis (UC). Prebiotic therapy is a potential approach for UC management especially remission maintaining. Xylo-oligosaccharide (XOS) is an efficient prebiotic with proven health benefits and few side effects. However, the effects of XOS on the gut microbiota of patients with UC have not been investigated previously. The aim of this study was to evaluate the prebiotic effects of XOS on the fecal microbiota of patients with UC in clinical remission using an in vitro fermentation model. Five patients with UC in clinical remission and five healthy volunteers were enrolled in this study. Fresh fecal samples of UC patients were diluted and inoculated in yeast extract, casitone and fatty acid (YCFA) medium alone or with XOS. After fermentation for 48 h, samples were collected for 16S rDNA sequencing to investigate the gut microbiota composition. Differences in the gut microbiota between healthy volunteers and UC patients in clinical remission were detected using original fecal samples. Subsequently, the differences between the YCFA medium alone or with XOS samples were analyzed to illustrate the effects of XOS on the gut microbiota of UC patients. In both principal coordinate analysis (PCoA) and principal component analysis (PCA), the fecal samples of UC patients differed from those of healthy volunteers. Linear discriminant analysis effect size (LEfSe) analysis revealed that the relative abundances of g_Roseburia and g_Lachnospiraceae_ND3007_group were higher in healthy volunteers than in UC patients, while o_Lactobacillales abundance showed the opposite trend (P < 0.05). Wilcoxon rank-sum test bar plot showed that the abundances of g_Eubacterium_halli_group and g_Lachnospiraceae_ND3007_group were higher in the healthy volunteers than in the UC patients (P < 0.05). In addition, in UC patients, the Wilcoxon rank-sum test showed that XOS fermentation promoted the growth of bacterial groups including g_Roseburia, g_Bifidobacterium, and g_Lactobacillus, which is beneficial for recovery of intestinal diseases. These results suggest that XOS can relieve dysbiosis in the feces of UC patients in clinical remission and thus represent a potential prebiotic material for maintaining remission.

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Amycomicin: a potent and specific antibiotic discovered with a targeted interaction screen

10.1101/317362 ◽

2018 ◽

Cited By ~ 1

Author(s):

Gleb Pishchany ◽

Emily Mevers ◽

Sula Ndousse-Fetter ◽

Dennis J. Horvath ◽

Camila R. Paludo ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Fatty Acid ◽

Small Molecule ◽

Pathogenic Bacteria ◽

Fatty Acid Biosynthesis ◽

Specific Inhibitor ◽

Mouse Skin ◽

Acid Biosynthesis ◽

Microbial Species ◽

Rdna Sequencing

AbstractThe rapid emergence of antibiotic-resistant pathogenic bacteria has accelerated the search for new antibiotics. Many clinically used antibacterials were discovered through culturing a single microbial species under nutrient-rich conditions, but in the environment, bacteria constantly encounter poor nutrient conditions and interact with neighboring microbial species. In an effort to recapitulate this environment we generated a nine-strain Actinomycete community and used 16S rDNA sequencing to deconvolute the stochastic production of antimicrobial activity that was not observed from any of the axenic cultures. We subsequently simplified the community to just two strains and identified Amycolatopsis sp. AA4 as the producing strain and Streptomyces coelicolor M145 as an inducing strain. Bioassay-guided isolation identified amycomicin, a highly modified fatty acid containing an epoxide isonitrile warhead as a potent and specific inhibitor of Staphylococcus aureus. Amycomicin targets an essential enzyme in fatty acid biosynthesis (FabH) and reduces S. aureus infection in a mouse skin infection model. The discovery of amycomicin demonstrates the utility of screening complex communities against specific targets to discover small-molecule antibiotics.SignificanceBacteria, especially actinomycetes, produce the majority of our clinically useful small-molecule antibiotics. Genomic analyses of antibiotic-producing strains indicate that earlier discovery efforts found only a fraction of the likely antibiotic candidates. In an effort to uncover these previously missed candidates we developed an approach that utilizes the ability of microbial communities to produce antibiotics that are not produced by any single member in isolation. Successful communities were established and deconvoluted to identify both producers and inducers of antibiotic activity. One inducer-producer pair made amycomicin, a potent and specific antibiotic against Staphylococcus aureus, an important human pathogen. Amycomicin targets fatty acid biosynthesis and exhibits in vivo efficacy against skin infections in a mouse model.

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Caloric restriction promotes functional changes involving short-chain fatty acid biosynthesis in the rat gut microbiota

Scientific Reports ◽

10.1038/s41598-018-33100-y ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 18

Author(s):

Alessandro Tanca ◽

Marcello Abbondio ◽

Antonio Palomba ◽

Cristina Fraumene ◽

Fabio Marongiu ◽

...

Keyword(s):

Fatty Acid ◽

Gut Microbiota ◽

Caloric Restriction ◽

Short Chain Fatty Acid ◽

Fatty Acid Biosynthesis ◽

Chain Fatty Acid ◽

Short Chain ◽

Acid Biosynthesis ◽

Functional Changes ◽

Rat Gut

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P054 Modulation of the Gut Microbiota-Farnesoid X Receptor Axis Improves Deoxycholic Acid-induced Intestinal Inflammation in Mice

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab076.183 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S161-S161

Author(s):

M Xu ◽

Y Shen ◽

M Cen

Keyword(s):

Bile Acid ◽

Gut Microbiota ◽

Intestinal Microbiota ◽

Acid Metabolism ◽

Deoxycholic Acid ◽

Intestinal Inflammation ◽

Farnesoid X Receptor ◽

Bile Acid Metabolism ◽

Gut Dysbiosis ◽

Rdna Sequencing

Abstract Background Inflammatory bowel disease (IBD) is associated with gut dysbiosis and dysregulation of bile acid metabolism. A high luminal content of deoxycholic acid (DCA) with consumption of a Westernized diet is implicated in the pathogenesis of IBD. The aim of the study is to explore the role of intestinal microbiota and bile acid metabolism in mice with DCA-induced intestinal inflammation. Methods 4-week-old wild-type C57BL mice were fed with AIN-93G (control diet), AIN-93G+0.2% DCA, AIN-93G+0.2% DCA+6 weeks of fexaramine (FXR agonist), or AIN-93G+0.2% DCA+antibiotic cocktail for 24 weeks. Histopathology, Western blotting, and qPCR were performed on the intestinal tissue. Fecal microbiota was analyzed by 16S rDNA sequencing. Fecal bile acid and short-chain fatty acid (SCFA) levels were analyzed by chromatography. Results Gut dysbiosis and enlarged bile acid pool were observed in DCA-treated mice, accompanied by a lower farnesoid X receptor (FXR) activity in the intestine. Administration of fexaramine mitigated DCA-induced intestinal injury, restored intestinal FXR activity, activated ﬁbroblast growth factor 15, and normalized bile acid metabolism. Furthermore, fexaramine administration increased the abundance of SCFA-producing bacteria. Depletion of the commensal microbiota with antibiotics decreased the diversity of the intestinal microbiota, attenuated bile acid synthesis, and reduced intestinal inflammation induced by DCA. Conclusion DCA induced-intestinal inflammation is associated with alterations of gut microbiota and bile acid proﬁles. Interventions targeting the gut microbiota-FXR signaling pathway may reduce DCA-induced intestinal disease.

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Saccharomyces boulardii alleviates ulcerative colitis carcinogenesis in mice by reducing TNF-α and IL-6 levels and functions and by rebalancing intestinal microbiota

BMC Microbiology ◽

10.1186/s12866-019-1610-8 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 12

Author(s):

Chunsaier Wang ◽

Wenbin Li ◽

Hongying Wang ◽

Yiming Ma ◽

Xinhua Zhao ◽

...

Keyword(s):

Ulcerative Colitis ◽

Treatment Group ◽

Intestinal Microbiota ◽

Treated Group ◽

Saccharomyces Boulardii ◽

Inhibition Mechanism ◽

Control Group ◽

Rdna Sequencing ◽

Tnf Α ◽

Tumor Load

Abstract Background and Aims To explore the inhibition mechanism of Saccharomyces boulardii (S. boulardii) on ulcerative colitis (UC) carcinogenesis. Methods C57BL/6 mice were treated with azoxymethane and dextran sulfate sodium (AOM/DSS) to develop a UC carcinogenesis model. The treatment group was lavaged with S. boulardii (5 × 107 CFU/d) for 12 weeks. The mice were sacrificed and the tumor load in the treatment group was compared with that of a control group. The levels of TNF-α and IL-6 in colon tissue were measured by enzyme-linked immunosorbent assays. The influence of S. boulardii on TNF-α and IL-6 regulation was also investigated using different colon cell lines. Differences in intestinal microbiota in both stool and intestinal mucosa samples were assessed using 16S rDNA sequencing. Results S. boulardii treatment reduced AOM/DSS-induced UC carcinogenesis in mice, as indicated by the reduced tumor load and reduced TNF-α and IL-6 levels in vivo, as well its effects on TNF-α and IL-6 activities in vitro. Significant changes in both fecal and mucosal microbiota were observed among the control, the AOM/DSS treated, and AOM/DSS plus S. boulardii treated groups. For fecal microbiota, the AOM/DSS treated group was lower in Lactobacillus, but higher in Oscillibacter and Lachnoclostridium than the control group. After intervention with S. boulardii, the percentage of Bacillus and Lactococcus increased, but Lachnoclostridium, Oscillibacter, Bacteroides, and Pseudomonas decreased. For the intestinal mucosal microbiota, the AOM/DSS treated group was lower in Bifidobacterium and Ruminococcaceae_UCG-014 and higher in Alloprevotella than the control group. After S. boulardii exposure, the percentage contributions of Lachnoclostridium and Lachnospiraceae_NK4A136 increased. Conclusions S. boulardii effectively reduced UC carcinogenesis in an AOM/DSS induced mice model. This positive result can likely be attributed to the reduction of TNF-α and IL-6 levels or the blockade of their function combined with alterations to the intestinal microbiota.

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Microbiome Analysis of Mucosal Ileoanal Pouch in Ulcerative Colitis Patients Revealed Impairment of the Pouches Immunometabolites

Cells ◽

10.3390/cells10113243 ◽

2021 ◽

Vol 10 (11) ◽

pp. 3243

Author(s):

Orazio Palmieri ◽

Stefano Castellana ◽

Giuseppe Biscaglia ◽

Anna Panza ◽

Anna Latiano ◽

...

Keyword(s):

Ulcerative Colitis ◽

Gut Microbiota ◽

Ileoanal Pouch ◽

Bacterial Strains ◽

Microbial Composition ◽

Novel Treatments ◽

Microbiome Analysis ◽

Unknown Species ◽

Healthy Control

The pathogenesis of ulcerative colitis (UC) is unknown, although genetic loci and altered gut microbiota have been implicated. Up to a third of patients with moderate to severe UC require proctocolectomy with ileal pouch ano-anastomosis (IPAA). We aimed to explore the mucosal microbiota of UC patients who underwent IPAA. Methods: For microbiome analysis, mucosal specimens were collected from 34 IPAA individuals. Endoscopic and histological examinations of IPAA were normal in 21 cases, while pouchitis was in 13 patients. 19 specimens from the healthy control (10 from colonic and 9 from ileum) were also analyzed. Data were analyzed using an ensemble of software packages: QIIME2, coda-lasso, clr-lasso, PICRUSt2, and ALDEx2. Results: IPAA specimens had significantly lower bacterial diversity as compared to normal. The microbial composition of the normal pouch was also decreased also when compared to pouchitis. Faecalibacterium prausnitzii, Gemmiger formicilis, Blautia obeum, Ruminococcus torques, Dorea formicigenerans, and an unknown species from Roseburia were the most uncommon in pouch/pouchitis, while an unknown species from Enterobacteriaceae was over-represented. Propionibacterium acnes and Enterobacteriaceae were the species most abundant in the pouchitis and in the normal pouch, respectively. Predicted metabolic pathways among the IPAA bacterial communities revealed an important role of immunometabolites such as SCFA, butyrate, and amino acids. Conclusions: Our findings showed specific bacterial signature hallmarks of dysbiosis and could represent bacterial biomarkers in IPAA patients useful to develop novel treatments in the future by modulating the gut microbiota through the administration of probiotic immunometabolites-producing bacterial strains and the addition of specific prebiotics and the faecal microbiota transplantation.

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